Abstract
Background: Klebsiella pneumonia has emerged as a critical pathogen causing severe clinical problems, such as pneumonia and sepsis. Meanwhile, intensified drug resistance induced by antibiotic therapy necessitates discovering novel and active molecules from Traditional Chinese Medicine (TCM) for treatment. Methods and results: In this study, the isolated Bergenin monohydrate showed an anti-inflammatory effect in Klebsiella-infected mice. We initially investigated the anti-inflammatory effects and cytoprotection against oxidative stress in vitro and in vivo. Interestingly, a specific dose of Bm can effectively ameliorate lung injury and suppress the expression of inflammatory cytokines such as TNF-α, IL-6, IL-1β and PEG2. Moreover, Bm was also shown to reduced the levels of MPO, MDA and increased SOD and GSH activities. Moreover, we assessed the intracellular signaling molecules including p38, ERK, JNK, IκB, NF-κB-p65 by western blotting and verified through MAPK and NF-κB pathways inhibition experiments. These results reveal that Bm executed its effects via the classical MAPK signaling pathway and NF-κB pathway. Conclusion: Given its underlying anti-inflammatory effect, Bm may be used as a promising therapeutic against Klebsiella-induced infection, thus providing a benefit for the future clinical therapy of pneumonia and medicine design.
Highlights
Klebsiella pneumoniae (Kp), a nonmotile, facultatively anaerobic, gram-negative, rod-shaped bacterium, can cause acute lung injury in humans and is considered an urgent health concern (Peteranderl et al, 2017; Zhang et al, 2018)
The minimum inhibitory concentration (MIC) of Bergenin monohydrate (Bm) was greater than 256 μg/ml, which indicated that Bm had no considerable effect on Kp growth (Supplementary Figure S1)
Bm protected RAW 264.7 cells from Kp infection (Figure 1C), and the protective efficacy increased with increasing Bm concentration
Summary
Klebsiella pneumoniae (Kp), a nonmotile, facultatively anaerobic, gram-negative, rod-shaped bacterium, can cause acute lung injury in humans and is considered an urgent health concern (Peteranderl et al, 2017; Zhang et al, 2018). For adults in which Kp was the primary isolate, it caused a mortality rate of up to 50% in respiratory tract infections, with only 52% survival (Zhang et al, 2018; Choby et al, 2020). Antibiotic administration remains a major strategy for treating Kp infections in the clinic (Bengoechea and Sa Pessoa, 2019). Kp has increasingly survived antibiotic treatment due to resistance or tolerance to the drugs. Klebsiella pneumonia has emerged as a critical pathogen causing severe clinical problems, such as pneumonia and sepsis. Intensified drug resistance induced by antibiotic therapy necessitates discovering novel and active molecules from Traditional Chinese Medicine (TCM) for treatment
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